A novel GH secretagogue, A233, exhibits enhanced growth activity and innate immune system stimulation in teleosts fish

Abstract

In teleosts fish, secretion of GH is regulated by several hypothalamic factors that are influenced by the physiological state of the animal. There is an interaction between immune and endocrine systems through hormones and cytokines. GH in fish is involved in many physiological processes that are not overtly growth related, such as saltwater osmoregulation, antifreeze synthesis, and the regulation of sexual maturation and immune functions. This study was conducted to characterize a decapeptide compound A233 (GKFDLSPEHQ) designed by molecular modeling to evaluate its function as a GH secretagogue (GHS). In pituitary cell culture, the peptide A233 induces GH secretion and it is also able to increase superoxide production in tilapia head-kidney leukocyte cultures. This effect is blocked by preincubation with the GHS receptor antagonist [D-Lys 3 ]-GHRP6. Immunoneutralization of GH by addition of anti-tilapia GH monoclonal antibody blocked the stimulatory effect of A233 on superoxide production. These experiments propose a GH-mediated mechanism for the action of A233. The in vivo biological action of the decapeptide was also demonstrated for growth stimulation in goldfish and tilapia larvae (P!0 . 001). Superoxide dismutase levels, antiprotease activity, and lectin titer were enhanced in tilapia larvae treated with this novel molecule. The decapeptide A233 designed by molecular modeling is able to function as a GHS in teleosts and enhance parameters of the innate immune system in the fish larvae.

Growth Hormone Secretagogue (A233) Improves Growth and Changes the Tissue Fatty Acid Profile in Juvenile Tilapia (Oreochromis niloticus)

“…The growth results agree with our previous report showing that the GH secretagogue peptide, A233, is able to stimulate growth when it is administered to tilapia larvae by immersion baths three times a week for 1 month (Martinez et al, ). We observed that the group fed with the diet supplemented with A233 had lower lipid content in the muscle, which is consistent with the observation that elevated circulating GH is associated with a reduction in intramuscular fat (Oberbauer et al, ).…”

“…GH is well known as the main growth regulator in mammals (Isaksson, Jansson, & Gause, ) and also influences, directly or indirectly, carbohydrate, lipid, nitrogen, and mineral metabolism (Davidson, ; Eisemann et al, ; Møller & Jørgensen, ). In a previous study, Martinez et al () demonstrated that A233 was able to function as a GHS in teleost fish larvae when administered by immersion. Here we report that inclusion of 600 μg kg –1 of the A233 peptide in juvenile tilapia feed (group 2) significantly improved growth and modified lipid deposition and FA content, as well as composition in the liver and muscle.…”

“…It was suggested that the action of A233 is mediated by the GHS receptor‐1 a (GHS‐R1 a ) (Martinez et al, ). This receptor mediates both adipogenic and orexigenic actions of GRLN (Davies et al, ) by the activation of AMP‐activated protein kinase, regulating fat distribution and metabolism in a tissue‐specific manner (Hardie, ).…”

“…The correct sequence of the purified peptide was confirmed by electrospray ionization mass spectrometry (Micromass, Manchester, UK). It was lyophilized and reconstituted in PBS 1X (NaCl 136 mmol/L, KH 2 PO 4 1.47 mmol/L, Na 2 HPO 4 9.55 mmol/L, KCl 2.68 mmol/L, pH = 7.4) (Martinez et al, ).…”

“…The molecule A233, a synthetic peptide mimetic of ghrelin (GRLN) (Martinez et al, ), was designed by the molecular modeling of the human ghrelin receptor (Rodriguez et al, ). This molecule is able to function as a GHS in teleosts and enhance the growth and parameters of the innate immune system in goldfish and tilapia larvae by immersion; we also demonstrated that the A233 effects were dependent on GH release (Martinez et al, ). In a recent study, we observed an increase in the level of enzymes from FA metabolism in a proteomic analysis of J774A.2 macrophage cells stimulated with A233 (Martínez et al, ).…”